Cytoprotective activities of kinetin purine isosteres

Maková, Barbara; Mik, Václav; Lišková, Barbora; González, Gabriel; Vítek, Dominik; Medvedíková, Martina; Monfort, Beata; Ručilová, Veronika; Kadlecová, Alena; Khirsariya, Prashant; Barreiro, Zoila Gándara; Havlı́cěk, Libor; Zatloukal, Marek; Soural, Miroslav; Paruch, Kamil; D’Autréaux, Benoît; Hajdúch, Marián; Strnad, Miroslav; Voller, Jiří

doi:10.1016/j.bmc.2021.115993

Cited by 6 publications

(6 citation statements)

References 54 publications

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“…Maková et al [129] reported the protective effects of synthetic kinetin bioisosteres against BSO-induced oxidative stress in fibroblasts derived from patients with FRDA. Synthesis of the novel compounds was achieved by replacing the purine ring with other bicyclic heterocycles.…”

Section: Histone Deacetylases Inhibitorsmentioning

confidence: 99%

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

et al. 2022

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Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of rare neurodegenerative inherited disorders. The resulting motor incoordination and progressive functional disabilities lead to reduced lifespan. There is currently no cure for ARCAs, likely attributed to the lack of understanding of the multifaceted roles of antioxidant defense and the underlying mechanisms. This systematic review aims to evaluate the extant literature on the current developments of therapeutic strategies that target oxidative stress for the management of ARCAs. We searched PubMed, Web of Science, and Science Direct Scopus for relevant peer-reviewed articles published from 1 January 2016 onwards. A total of 28 preclinical studies fulfilled the eligibility criteria for inclusion in this systematic review. We first evaluated the altered cellular processes, abnormal signaling cascades, and disrupted protein quality control underlying the pathogenesis of ARCA. We then examined the current potential therapeutic strategies for ARCAs, including aromatic, organic and pharmacological compounds, gene therapy, natural products, and nanotechnology, as well as their associated antioxidant pathways and modes of action. We then discussed their potential as antioxidant therapeutics for ARCAs, with the long-term view toward their possible translation to clinical practice. In conclusion, our current understanding is that these antioxidant therapies show promise in improving or halting the progression of ARCAs. Tailoring the therapies to specific disease stages could greatly facilitate the management of ARCAs.

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Section: Histone Deacetylases Inhibitorsmentioning

confidence: 99%

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

et al. 2022

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“…ATRA‐differentiated SH‐SY5Y cells were co‐treated with Glu and newly prepared compounds in selected concentrations alongside R ‐lipoic acid ( R ‐LA) (0.5; 5; 50 µM) as a positive control [ 66 ] for 24 h, as described previously. [ 73 ] After 24 h treatment, the protective effect of studied derivatives was determined by propidium iodide cell death assay. Data were normalized to cell death induced by 160 mM Glu, set as 100%.…”

Section: Resultsmentioning

confidence: 99%

“…These results confirm the neuroprotective effect of compound 28 and R ‐LA, which is in accordance with the literature. [ 73,75 ] Noteworthy, compound 28 outperformed positive control due to five‐fold lower active concentration and slightly better drop in LDH release. As compound 28 was found to be active in both cellular models of neurodegeneration, it was further investigated for its activity under oxidative stress and caspase‐3/7 activity within Glu model.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis and neuroprotective activity of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives

Šachlevičiūtė,

Gonzalez,

Kvasnicová

et al. 2023

Archiv der Pharmazie

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A library of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives was prepared from N‐Boc‐3‐azetidinone employing the Horner‐Wadsworth‐Emmons reaction, rhodium(I)‐catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N‐unprotected hydrochlorides, N‐alkylated and N‐acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol‐induced) and aspects of Alzheimer's disease (glutamate‐induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol‐ and glutamate‐induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase‐3/7 activity.

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“…Both cultivars presented numerous metabolites covering the classes of terpenes, such as limonene; terpenoids, such as apiole and phytuberin; hormones (cis-zeatin- O -glucoside); flavonoids (myricetin, cyanidin 3-4′′-acetylglucoside, quercetin 3-galactoside [ 32 ], flavonol 3- O - d -glycoside, apigenin-rhamnoside-rutinoside); vitamins (retinoic acid and pantothenic acid); nucleosides (dimethyladenosine, orotidine, methylguanosine); alkaloids (theophylline, nicotine, and caffeine). Furthermore, a precursor of lignins and lignols (caffeyl alcohol) were also identified in Goji berries, along with kinetin, a phytohormone able to modulate some aging-related disorders in animal models [ 33 ], revealed exclusively in the BL cultivar.…”

Section: Resultsmentioning

confidence: 99%

Metabolomic Profiling of Fresh Goji (Lycium barbarum L.) Berries from Two Cultivars Grown in Central Italy: A Multi-Methodological Approach

et al. 2021

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The metabolite profile of fresh Goji berries from two cultivars, namely Big Lifeberry (BL) and Sweet Lifeberry (SL), grown in the Lazio region (Central Italy) and harvested at two different periods, August and October, corresponding at the beginning and the end of the maturation, was characterized by means of nuclear magnetic resonance (NMR) and electrospray ionization Fourier transform ion cyclotron resonance (ESI FT-ICR MS) methodologies. Several classes of compounds such as sugars, amino acids, organic acids, fatty acids, polyphenols, and terpenes were identified and quantified in hydroalcoholic and organic Bligh-Dyer extracts. Sweet Lifeberry extracts were characterized by a higher content of sucrose with respect to the Big Lifeberry ones and high levels of amino acids (glycine, betaine, proline) were observed in SL berries harvested in October. Spectrophotometric analysis of chlorophylls and total carotenoids was also carried out, showing a decrease of carotenoids during the time. These results can be useful not only to valorize local products but also to suggest the best harvesting period to obtain a product with a chemical composition suitable for specific industrial use. Finally, preliminary studies regarding both the chemical characterization of Goji leaves generally considered a waste product, and the biological activity of Big Lifeberry berries extracts was also investigated. Goji leaves showed a chemical profile rich in healthy compounds (polyphenols, flavonoids, etc.) confirming their promising use in the supplements/nutraceutical/cosmetic field. MG63 cells treated with Big Lifeberry berries extracts showed a decrease of iNOS, COX-2, IL-6, and IL-8 expression indicating their significant biological activity.

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Cytoprotective activities of kinetin purine isosteres

Cited by 6 publications

References 54 publications

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

Synthesis and neuroprotective activity of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives

Metabolomic Profiling of Fresh Goji (Lycium barbarum L.) Berries from Two Cultivars Grown in Central Italy: A Multi-Methodological Approach

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